Paroxysmal central nervous system disorders

Region: ISCA-37468-Loss

Xp11.23 region (includes MAOA and MAOB) Loss

Red List (low evidence)

Chromosome: X
GRCh38 Position: 43654906-43882474
Haploinsufficiency Score: Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Triplosensitivity Score:
Required percent of overlap: 80%
Variant types: CNV Loss

1 review

Rebecca Foulger (Genomics England curator)

Red List (low evidence)

Comment on list classification: Demoted CNV from Green to Red based on GLH review and a recent comment (September 30th 2019) from Robyn Labrum (University College London Hospitals) collated on behalf of London North GLH for the GMS Neurology specialist test group: Inappropriate phenotype. Better suited to ataxia panels, epilepsy or muscular dystrophy panel.
Created: 1 Oct 2019, 12:34 p.m. | Last Modified: 1 Oct 2019, 12:34 p.m.
Panel Version: 0.167
Review and rating from Penny Clouston (Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust) was collated (September 19th 2019) on behalf of West Midlands, Oxford and Wessex GLH for the GMS Neurology specialist test group. Re-review of a subset of entities was conducted in September 2019 to reach a rating consensus for clinical indication R66: Paroxysmal central nervous system disorders. Symbol submitted: ISCA-37468-Loss. Suggested rating: Red; Comments provided: None.
Created: 23 Sep 2019, 10:18 a.m. | Last Modified: 23 Sep 2019, 10:18 a.m.
Panel Version: 0.94
Review and rating from Robyn Labrum (University College London Hospitals) was collated (September 19th 2019) on behalf of London North GLH for the GMS Neurology specialist test group. Re-review of a subset of entities was conducted in September 2019 to reach a rating consensus for clinical indication R66: Paroxysmal central nervous system disorders. Symbol submitted: ISCA-37468-Loss. Suggested rating: Red; Comments provided: phenotype severe and complicated, also episodes of sudden loss of muscle tone may occur. It may be better on another panel? Intellectual disability?.
Created: 23 Sep 2019, 9:53 a.m. | Last Modified: 23 Sep 2019, 9:54 a.m.
Panel Version: 0.94
Review and rating from James Polke (Neurogenetics Laboratory, Institute of Neurology, London), collated (February 2019) on behalf of London North GLH for the GMS Neurology specialist test group. Symbol submitted: ISCA-37468-Loss; Suggested initial gene rating: Red; Evidence: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided.
Created: 2 Sep 2019, 3:08 p.m. | Last Modified: 2 Sep 2019, 3:45 p.m.
Panel Version: 0.28

Details

ISCA ID
ISCA-37468-Loss
ISCA Region Name
Xp11.23 region (includes MAOA and MAOB) Loss
Chromosome
X
GRCh38 Coordinates
43654906-43882474
Haploinsufficiency Score
Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Triplosensitivity Score
Required percent of overlap
80%
Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
Phenotypes
  • short stature
  • severe intellectual disability
  • lip-smacking
  • exiting behavior
  • autistic features
  • hypotonia
  • stereotypical hand movements
  • eleveated serotonin levels
  • episodes of sudden loss of muscle tone
Clinvar variants
Variants in
Penetrance
None
Variant types
CNV Loss
Publications

History Filter Activity

1 Oct 2019, Gel status: 1

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Region: isca-37468-loss has been classified as Red List (Low Evidence).

17 Sep 2019, Gel status: 3

Changed Triplosensitivity Score, Added New Source

Rebecca Foulger (Genomics England curator)

Triplosensitivity Score for ISCA-37468-Loss was changed from None to . Source London North GLH was added to Region: ISCA-37468-Loss.

2 Sep 2019, Gel status: 3

Changed Triplosensitivity Score, Removed Source, Added New Source, Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Triplosensitivity Score for ISCA-37468-Loss was changed from to None. Source London North GLH was removed from Region: ISCA-37468-Loss. Source NHS GMS was added to Region: ISCA-37468-Loss. Model of inheritance for Region: ISCA-37468-Loss was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than females) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

2 Sep 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source London North GLH was added to Region: ISCA-37468-Loss.

3 Jan 2019, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Region: ISCA-37468-Loss was added Region: ISCA-37468-Loss was added to Paroxysmal neurological disorders, pain disorders and sleep disorders. Sources: Expert Review Green Mode of inheritance for Region: ISCA-37468-Loss was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than females) Publications for Region: ISCA-37468-Loss were set to 20485326; 22365943; 23414621 Phenotypes for Region: ISCA-37468-Loss were set to short stature; severe intellectual disability; lip-smacking; exiting behavior; autistic features; hypotonia; stereotypical hand movements; eleveated serotonin levels; episodes of sudden loss of muscle tone